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Introduction: This study investigates the incidence, clinical characteristics, and treatment response of macular neovascularization (MNV) occurring after retinal pigment epithelium (RPE) and choroid graft translocation surgery (RPE-choroid TS). Methods: Retrospective analysis of 36 eyes of 36 consecutive patients who underwent RPE-choroid TS. Longer term follow-up of graft survival focusing on the occurrence of MNV was performed using multimodal imaging. Results: Indications for RPE-choroid TS included complications of neovascular age-related macular degeneration in 34 patients and drusenoid pigment epithelial detachment in 2 patients. With a mean follow-up of 30 months, 8 patients out of 36 developed signs of MNV. Of these 8 patients, 4 presented with a drop in visual acuity (VA) due to centrally located type 3 MNV. Early diagnosis and treatment prevented significant functional consequences. Four patients developed type 2 MNV at the border of the graft, which did not tend to affect the VA. Conclusion: We report a high incidence of MNV after RPE-choroid TS. Early diagnosis and treatment may preserve function in these patients. The type of MNV and location can be used to guide the management.

Objective Urine self-sampling has gained increasing interest for cervical cancer screening. In contrast to analytical performance, little information is available regarding the clinical accuracy for high-risk Human Papillomavirus (hrHPV) testing on urine. Methods VALHUDES is a diagnostic test accuracy study comparing clinical accuracy to detect high-grade cervical precancer (CIN2+) of HPV testing on self-collected compared to clinician-collected samples ( NCT03064087 ). Disease outcome was assessed by colposcopy and histology. The Abbott RealTime High Risk HPV assay performance was evaluated on Colli-Pee collected first-void urine with cervical outcomes as comparator. Results As no assay cut-off for urine has been clinically validated, we used the predefined cut-off for cervical samples (CN ≤ 32). Using this cut-off, hrHPV testing was similarly sensitive (relative sensitivity 0.95; 95% CI: 0.88–1.01) and specific (relative specificity 1.03; 95% CI: 0.95–1.13) for detection of CIN2+ compared to testing cervical samples. In the subgroup of women of 30 years and older, similar relative sensitivity (0.97; 95% CI: 0.89–1.05) and specificity (1.02; 95% CI: 0.93–1.12) was found. Additionally, an exploratory cut-off (CN ≤ 33.86) was defined which further improved sensitivity and analytical test performance. Conclusion HrHPV-DNA based PCR testing on home-collected first-void urine has similar accuracy for detecting CIN2+ compared to cervical samples taken by a clinician.

Background Interventions to reach women who do not participate regularly in screening may reduce the risk of cervical cancer. Self-collection of a vaginal specimen has been shown to increase participation. The relative clinical accuracy of human papillomavirus (HPV) testing on first-void urine (with Colli-Pee) and on vaginal self-samples versus on cervical clinician-collected samples is being investigated in the VALHUDES trial. The current study assesses attitudes and experiences regarding self-sampling among women enrolled in VALHUDES. Methods Questionnaires from 515 women (age 25–64 years [N = 498]; N = 10], age ≥ 65 [N = 3], enrolled between December 2017 - January 2020) referred to colposcopy because of previous cervical abnormalities and enrolled in VALHUDES (NCT03064087) were analysed. Results Of the 515 participants, nearly all women confirmed that self-sampling may help in reaching under-screened women (93%). Nevertheless, 44% of the participants stated before starting collection that a clinician-collected sample is more effective than a self-collected sample. After self-sampling, the large majority of women (> 95%) declared that instructions for self-collection were clear, that collection was easy, and that they were confident about having performed the procedure correctly, for both urine and vaginal collection. However, a proportion of women found self-sampling unpleasant (9.5% [49/515] for urine collection; 18.6% [96/515] and 15.5% [80/515] for vaginal sampling with cotton swabs or plastic brushes, respectively). For their next screening round, 57% would prefer self-sampling whereas 41% opted for collection by a clinician. Among women preferring self-sampling, 53% would choose for urine collection, 38% for vaginal self-collection and 9% had no preference. Age did not modify preferences. Conclusion We conclude that both urine and vaginal self-sampling are well accepted by women, with a preference for urine sampling. Although the large majority of women are confident in their ability to perform self-sampling, four to five over ten women preferred specimen collection by a clinician. Trial registration The study VALHUDES was registered in ClinicalTrials.gov (identifier: NCT03064087).

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

Combining myocardial perfusion single photon emission computed tomography (SPECT-MPI) and coronary computed tomography angiography (CCTA) is an interesting hybrid imaging option in modern cardiovascular medicine. The integrated hybrid technique has a number of advantages compared to visual side-by-side analysis of the separate modalities. CT attenuation map can correct for attenuation artefacts and thus improve the diagnostic accuracy of SPECT-MPI. Moreover, the anatomical information of the CCTA and the perfusion map of SPECT-MPI allow for vessel-based correlation and culprit vessel identification. Combining SPECT-MPI with CCTA is an appealing tool in the work-up of complex ischaemic heart disease and might help determine the optimal treatment strategy. This case series illustrates the role of SPECT-CCTA in decision-making of revascularization strategy in complex ischaemic heart disease.

Gender dysphoria, a discrepancy between gender identity and genetically determined sex, is encountered in approximately 0.5% of people uniformly across the world. In the case of transgender men, formerly called female-to-male transsexuals, the available gender-affirming measures, hormone therapy and possible surgical procedures, are multiple and discussed in detail in this series of articles.

Research question Is implantation impaired in patients with endometriosis undergoing IVF and intracytoplasmatic sperm injection (ICSI) cycles? Design A retrospective matched cohort study was carried out on IVF/ICSI cycles with fresh single embryo transfer at the Department of Assisted Reproductive Medicine, Ghent University Hospital, Belgium, between July 2015 and August 2017 (n = 1053). A total of 118 endometriosis cases were matched 1:1 to 118 couples diagnosed with male subfertility and stratified by embryo quality (identical ALPHA grading categories), female age (±1 year) and parity (±1 delivery). Transvaginal ultrasound, magnetic resonance imaging or laparoscopy was used to diagnosed endometriosis, and the revised American Society for Reproductive Medicine score was used to classify the endometriosis into grade I/II versus grade III/IV. Male subfertility was defined in accordance with World Health Organization criteria (fifth edition). Results Compared with endometriosis cases, control couples with male subfertility had significantly higher rates of positive HCG test on day 16 (P = 0.047, OR 2.077, CI 1.009 to 4.276), ongoing implantation (defined as a positive fetal heart rate on transvaginal ultrasound at a gestational age of at least 6.5–7 weeks) (P = 0.038, OR 2.265, CI 1.048 to 4.893), ongoing pregnancy (defined by a vital pregnancy at 11 weeks) (P = 0.046, OR 2.292, CI 1.016 to 5.173) and live birth (P = 0.043, OR 2.502, CI 1.029 to 6.087). Conclusions After matching for embryo quality, woman's age and parity, rates of positive HCG tests, ongoing implantation, ongoing pregnancy and live birth were more than twice as high in the control group compared with the endometriosis group.

Cystic fibrosis is a lethal inherited disease that affects multiple organs. To provide optimal pharmacological treatment of comorbidities associated with cystic fibrosis, relevant alterations in pharmacokinetics must be known. The objective of this study was to compare the pharmacokinetics of drugs between patients with cystic fibrosis and controls, based on clinical study reports published from 1999 to 2019. Clinical studies were considered if patients with cystic fibrosis and patients without cystic fibrosis/healthy volunteers were included, a drug was administered orally/intravenously and pharmacokinetic parameters were compared. In total, 32 clinical studies were included. Twenty-one studies reported absorption parameters. For multiple drugs, speed and/or extent of oral absorption were lower in cystic fibrosis. This phenomenon is possibly related to pathophysiological changes in the gastrointestinal tract associated with cystic fibrosis. However, a large proportion of drugs had comparable absorption kinetics. Twenty-one studies discussed volume of distribution, which was comparable between groups for most drugs. Initial differences became smaller when scaled to body composition. For some highly protein-bound drugs, inflammation-related changes in plasma proteins helped explain residual variability between cystic fibrosis and controls. Twenty-four studies elaborated on clearance, whereby higher clearances were observed in cystic fibrosis. In contrast with previously published reviews, no evidence was found for increased activities of drug-metabolising enzymes nor for up-regulation of active transport processes involved in drug disposition. In most cases, scaling clearance parameters to body composition and/or incorporating differences in plasma protein concentration accounted for these larger clearances. There is no evidence that genetic defects causing cystic fibrosis directly lead to altered pharmacokinetics. However, co-morbidities can have a potential impact on drug absorption and disposition. Because of gastrointestinal complications, it is not advisable to extrapolate drug absorption parameters from healthy volunteers to patients with cystic fibrosis. Differences observed in the volume of distribution and clearance in patients with cystic fibrosis can potentially be explained by correcting for lean body mass.

BACKGROUND: Although combination formulas containing antihistamines, decongestants, and/or analgesics are sold over‐the‐counter in large quantities for the common cold, the evidence for their effectiveness is limited. This is an update of a review first published in 2012. OBJECTIVES: To assess the effectiveness of antihistamine‐decongestant‐analgesic combinations compared with placebo or other active controls (excluding antibiotics) in reducing the duration of symptoms and alleviating symptoms (general feeling of illness, nasal congestion, rhinorrhoea, sneezing, and cough) in children and adults with the common cold. SEARCH METHODS: We searched CENTRAL, MEDLINE via EBSCOhost, Embase, CINAHL via EBSCOhost, LILACS, and Web of Science to 10 June 2021. We searched the WHO ICTRP and ClinicalTrials.gov on 10 June 2021. SELECTION CRITERIA: Randomised controlled trials investigating the effectiveness of antihistamine‐decongestant‐analgesic combinations compared with placebo, other active treatment (excluding antibiotics), or no treatment in children and adults with the common cold. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. We categorised the included trials according to the active ingredients. MAIN RESULTS: We identified 30 studies (6304 participants) including 31 treatment comparisons. The control intervention was placebo in 26 trials and an active substance (paracetamol, chlorphenindione + phenylpropanolamine + belladonna, diphenhydramine) in six trials (two trials had placebo as well as active treatment arms). Reporting of methods was generally poor, and there were large differences in study design, participants, interventions, and outcomes. Most of the included trials involved adult participants. Children were included in nine trials. Three trials included very young children (from six months to five years), and five trials included children aged 2 to 16. One trial included adults and children aged 12 years or older. The trials took place in different settings: university clinics, paediatric departments, family medicine departments, and general practice surgeries. Antihistamine‐decongestant: 14 trials (1298 participants). Eight trials reported on global effectiveness, of which six studies were pooled (281 participants on active treatment and 284 participants on placebo). The odds ratio (OR) of treatment failure was 0.31 (95% confidence interval (CI) 0.20 to 0.48; moderate certainty evidence); number needed to treat for an additional beneficial outcome (NNTB) 3.9 (95% CI 3.03 to 5.2). On the final evaluation day (follow‐up: 3 to 10 days), 55% of participants in the placebo group had a favourable response compared to 70% on active treatment. Of the two trials not pooled, one showed some global effect, whilst the other showed no effect. Adverse effects: the antihistamine‐decongestant group experienced more adverse effects than the control group: 128/419 (31%) versus 100/423 (13%) participants suffered one or more adverse effects (OR 1.58, 95%CI 0.78 to 3.21; moderate certainty of evidence). Antihistamine‐analgesic: four trials (1608 participants). Two trials reported on global effectiveness; data from one trial were presented (290 participants on active treatment and 292 participants on ascorbic acid). The OR of treatment failure was 0.33 (95% CI 0.23 to 0.46; moderate certainty evidence); NNTB 6.67 (95% CI 4.76 to 12.5). Forty‐three per cent of participants in the control group and 70% in the active treatment group were cured after six days of treatment. The second trial also showed an effect in favour of the active treatment. Adverse effects: there were not significantly more adverse effects in the active treatment group compared to placebo (drowsiness, hypersomnia, sleepiness 10/152 versus 4/120; OR 1.64 (95 % CI 0.48 to 5.59; low certainty evidence). Analgesic‐decongestant: seven trials (2575 participants). One trial reported on global effectiveness: 73% of participants in the analgesic‐decongestant group reported a benefit compared with 52% in the control group (paracetamol) (OR of treatment failure 0.28, 95% CI 0.15 to 0.52; moderate certainty evidence; NNTB 4.7). Adverse effects: the decongestant‐analgesic group experienced significantly more adverse effects than the control group (199/1122 versus 75/675; OR 1.62 95% CI 1.18 to 2.23; high certainty evidence; number needed to treat for an additional harmful outcome (NNTH 17). Antihistamine‐analgesic‐decongestant: six trials (1014 participants). Five trials reported on global effectiveness, of which two studies in adults could be pooled: global effect reported with active treatment (52%) and placebo (34%) was equivalent to a difference of less than one point on a four‐ or five‐point scale; the OR of treatment failure was 0.47 (95% CI 0.33 to 0.67; low certainty evidence); NNTB 5.6 (95% CI 3.8 to 10.2). One trial in children aged 2 to 12 years, and two trials in adults found no beneficial effect. Adverse effects: in one trial 5/224 (2%) suffered adverse effects with the active treatment versus 9/208 (4%) with placebo. Two other trials reported no differences between treatment groups. AUTHORS' CONCLUSIONS: We found a lack of data on the effectiveness of antihistamine‐analgesic‐decongestant combinations for the common cold. Based on these scarce data, the effect on individual symptoms is probably too small to be clinically relevant. The current evidence suggests that antihistamine‐analgesic‐decongestant combinations have some general benefit in adults and older children. These benefits must be weighed against the risk of adverse effects. There is no evidence of effectiveness in young children. In 2005, the US Food and Drug Administration issued a warning about adverse effects associated with the use of over‐the‐counter nasal preparations containing phenylpropanolamine.

Lay Summary Influenza is usually diagnosed clinically. However, the accuracy of a diagnosis of influenza based on clinical features is limited because symptoms overlap considerably with those caused by other microorganisms. This study examined whether identification of the severity rather than the presence of key signs and symptoms could aid in the diagnosis of influenza, thereby helping clinicians to determine when antiviral agent use is appropriate. The authors used the database of a previous randomized clinical trial on the effectiveness of an antiviral carried out in primary care centers in 15 countries in Europe during three epidemic periods from 2015/2016 to 2017/2018. Participants with influenza symptoms were included and they were asked about the presence and severity of different symptoms during the baseline visit with their doctors and a nasopharyngeal swab was taken for microbiological analysis. Overall, only 51% of the patients aged 18 or older had a confirmed influenza infection. Clinical findings are not particularly useful for confirming or excluding the diagnosis of influenza. However, the results of our study recommend considering how intense the different symptoms are, since key symptoms rated as moderate or severe are slightly better for predicting flu rather than the presence or absence of these symptoms. Background Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. Objective We evaluated the diagnostic value of the presence and the severity of symptoms for the diagnosis of laboratory-confirmed influenza infection among adults presenting with influenza-like illness (ILI) in primary care. Methods Secondary analysis of patients with ILI who participated in a clinical trial from 2015 to 2018 in 15 European countries. Patients rated signs and symptoms as absent, minor, moderate, or major problem. A nasopharyngeal swab was taken for microbiological identification of influenza and other microorganisms. Models were generated considering (i) the presence of individual symptoms and (ii) the severity rating of symptoms. Results A total of 2,639 patients aged 18 or older were included in the analysis. The mean age was 41.8 +/- 14.7 years, and 1,099 were men (42.1%). Influenza was microbiologically confirmed in 1,337 patients (51.1%). The area under the curve (AUC) of the model for the presence of any of seven symptoms for detecting influenza was 0.66 (95% confidence interval [CI]: 0.65-0.68), whereas the AUC of the symptom severity model, which included eight variables-cough, fever, muscle aches, sweating and/or chills, moderate to severe overall disease, age, abdominal pain, and sore throat-was 0.70 (95% CI: 0.69-0.72). Conclusion Clinical prediction of microbiologically confirmed influenza in adults with ILI is slightly more accurate when based on patient reported symptom severity than when based on the presence or absence of symptoms.

Objective: The aim of this study is to explore whether specific ethical questions arise with the use of a shared electronic health record (EHR) system, based on the daily experience of primary care physicians (PCPs). Methods: In this qualitative research project, we conducted 14 in-depth semistructured interviews with PCPs in a tertiary hospital setting. Results: We identified 4 themes: 1) PCPs describe the EHR as a medicine with side effects, for which they provide suggestions for improvements; 2) A shared record raises ethical questions related to autonomy and trust; 3) Although use of the EHR often disturbs rapport with the patient, it can also support the patient-doctor interaction when it becomes an active part of the conversation; 4) A shared EHR may cause health care providers (and their relatives) to avoid seeking help for sensitive issues. Discussion: PCPs fear access to results could cause confusion and anxiety in patients, resulting in tensions between autonomy and beneficence. Improved efficiency and quality of care with a shared EHR relies on doctors trusting each other9s input to avoid duplicate tests. However, this might compromise a fundamental skeptical attitude in practicing medicine, and we should be aware of a risk of increased confirmation and anchoring bias. Conclusion: The EHR is considered to be a work in progress—EHR design could be improved by examining physicians9 coping strategies and implementing their suggestions for improvement. Ethical questions related to autonomy, trust, and the status of records that belong to doctor–patients need to be considered in future research and EHR development.

It has been well established that low-density lipoproteins (LDL) and other apolipoprotein B-containing lipoproteins are causally related to atherosclerotic cardiovascular disease (ASCVD) and that lowering these lipoproteins reduces the risk of ASCVD. By lowering LDL particles as much as possible, ASCVD can be prevented. There seems to be no LDL-cholesterol (LDL-C) threshold below which no further ASCVD prevention can be achieved. Furthermore, a low (an even very low) LDL-C appears to be safe. The new ESC/EAS guidelines based on these concepts are a step towards a benefit-based strategy by focusing on the clinical benefit that can be achieved by treating the cause of ASCVD. It is recommended to lower LDL-C as much as possible to prevent ASCVD, especially in high and very high-risk patients. With these new recommendations come recognition of the importance of combination therapies in high and very high-risk patients, first with statins and ezetimibe, and if needed with a PCSK9 inhibitor. The present paper is a review of some new concepts arising during the past 10 years in the field of lipidology and the description of what is new in the 2019 EAS/ESC guidelines. ispartof: ACTA CLINICA BELGICA vol:75 issue:1 pages:80-90 ispartof: location:England status: published

Objective To investigate the extent to which assisted oocyte activation (AOA) improves clinical outcomes in patients diagnosed with oocyte activation deficiencies (OADs). Design Retrospective cohort study comparing AOA cycles and previous intracytoplasmic sperm injection (ICSI) cycles in couples experiencing low or total failed fertilization after ICSI. Importantly, the sperm-related oocyte-activating capacity was examined in all patients before AOA with the use of the mouse oocyte activation test (MOAT). Setting Infertility center at a university hospital. Patient(s) A total of 122 couples with a history of low or total failed fertilization after ICSI. Intervention(s) ICSI, MOAT, AOA, and embryo transfer. Main Outcome Measure(s) Fertilization, pregnancy, and live birth rates. Result(s) MOAT revealed 19 patients with a sperm-related OAD (MOAT group 1), 56 patients with a diminished sperm-related oocyte-activating capacity (MOAT group 2), and 47 patients with a suspected oocyte-related OAD (MOAT group 3). AOA (191 cycles) significantly improved fertilization, pregnancy, and live birth rates in all MOAT groups compared with previous ICSI attempts (243 cycles). Fertilization rates after AOA were significantly different among MOAT groups 1 (70.1%), 2 (63.0%), and 3 (57.3%). Between MOAT group 1 and 3, significant differences in pregnancy (49.0% vs. 29.4%) and live birth (41.2% vs. 22.1%) rates were observed. In total, 225 embryo transfers resulted in 60 healthy live births following AOA. Conclusion(s) Patients undergoing diagnostic testing before AOA show a significant improvement in clinical outcomes compared with previous cycles. Our findings highlight that AOA should be reserved for patients with clear OADs.

Purpose The importance of the surrounding ovarian stromal cells and extracellular matrix in the development and maturation of follicles has recently gained attention. An aberrant extracellular matrix has been described in ovaries of patients with polycystic ovary syndrome where a more rigid structural environment, possibly induced by endogenous testosterone, impairs normal folliculogenesis. In this context, we describe the textural parameters of the ovarian cortex of transgender men after prolonged testosterone administration compared to the textural parameters of the non-exposed ovarian cortex originating from female oncological patients. Methods Texture profile analysis (TPA) was performed on ovarian cortex (5 × 5 mm) of oncological and transgender patients in order to measure stiffness, hardness, cohesiveness, and springiness of the ovarian cortex (LRXplus universal testing system). Statistical analysis was performed using repeated measurements mixed models and the Spearman rank order correlation test (IBM SPSS Statistics 23). Results A total of 36 frozen-thawed cortical strips (5 × 5 mm) were subjected to TPA. The superficial part of cortex fragments originating from transgender persons (fragments < 1.4 mm; N = 10) appeared to be significantly stiffer compared to cortex derived from oncology patients (fragments < 1.4 mm; N = 7) (6.78 ± 1.38 N/mm versus 5.41 ± 0.9 N/mm respectively, p = 0.036). Conclusions This is the first application of TPA in ovarian cortex to study the physical properties. Comparing the physical properties, we objectively describe an increased cortical stiffness in the most outer part of the ovarian cortex following prolonged testosterone administration in transgender men compared to the ovarian cortex of oncological patients. This preliminary and novel approach could be the start of future research to understand the physical properties of ovarian tissue. Electronic supplementary material The online version of this article (10.1007/s10815-019-01513-x) contains supplementary material, which is available to authorized users.

Inadequacies exist in the ergonomics of upper body positioning of robotic surgeons; these deficits in biomechanical efficacy predispose surgeons to musculoskeletal injury. Ergonomics and biomechanics may be objectively measured using the Rapid Entire Body Assessment (REBA) and the Rapid Upper Limb Assessment (RULA) to quantify ergonomic efficacy. The purpose of this study is to use validated ergonomic tools to assess the posture of robotic surgeons to examine deficiencies. Four robotic surgeons using the da Vinci model were observed for a minimum of 30 min each. An Xbox connect camera was positioned 10 feet away from the surgeon console. Kinetisense software measured position of the head, shoulders, mid-spine, hips, and knees. One image was captured every 30 s. The software measured the positions in centimeters that deviated from an ideal central postural line (plumb line). RULA and REBA were also employed to assess posture using a still image at 15 min. The average RULA score for the four surgeons was 4.75 (range 3-6). The average REBA score for the four surgeons was 7 (range 5-8). The average RULA score of 4.5/7 and the average REBA of 7/15 qualify as medium risk with the recommendation that action is needed to improve ergonomics. While this pilot study is limited in size, it demonstrates the need for further investigation. With more than half of surgeons reporting musculoskeletal pain after robotic surgery (McDonald et al. in Gynecol Oncol 134:243-247, 2014), poor posture may offer an explanation.

Objective: To develop a random forest model (RFM) to predict implantation potential of a transferred embryo and compare it with a multivariate logistic regression model (MvLRM), based on data from a large cohort including in vitro fertilization (IVF) patients treated with the use of single-embryo transfer (SET) of blastocyst-stage embryos. Design: Retrospective study of a 2-year single-center cohort of women undergoing IVF or intracytoplasmatic sperm injection (ICSI). Setting: Academic hospital. Patient(s): Data from 1,052 women who underwent fresh SET in IVF or ICSI cycles were included. Intervention(s): None. Main Outcome Measure(s): The performance of both RFM and MvLRM to predict pregnancy was quantified in terms of the area under the receiver operating characteristic (ROC) curve (AUC), classification accuracy, specificity, and sensitivity. Result(s): ROC analysis resulted in an AUC of 0.74 ± 0.03 for the proposed RFM and 0.66 ± 0.05 for the MvLRM for the prediction of ongoing pregnancies of ≥11 weeks. This RFM approach and the MvLRM yielded, respectively, sensitivities of 0.84 ± 0.07 and 0.66 ± 0.08 and specificities of 0.48 ± 0.07 and 0.58 ± 0.08. Conclusion(s): The performance to predict ongoing implantation will significantly improve with the use of an RFM approach compared with MvLRM.

IntroductionNational severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence data provides essential information about population exposure to the virus and helps predict the future course of the epidemic. Early cohort studies have suggested declines in levels of antibodies in individuals, associated with, for example, illness severity, age and co-morbidities. This protocol focuses on the seroprevalence among primary health care providers (PHCPs) in Belgium. They manage the vast majority of COVID-19 patients in addition to other patients and therefore play an essential role in the efficient organisation of health care. Currently, evidence is lacking on 1. how many PHCPs get infected with SARS-CoV-2 in Belgium, 2. the rate at which this happens, 3. their clinical spectrum, 4. their risk factors, 5. the effectiveness of the measures to prevent infection and 6. the accuracy of the serology-based point-of-care test in a primary care setting.Methods and analysisThis study will be set up as a prospective cohort study. General practitioners (GPs) and other PHCPs (working in a GP practice) will be recruited via professional networks and professional media outlets to register online to participate. Registered GPs and other PHCPs will be asked at each testing point (n=9) to perform a capillary blood sample antibody point-of-care test (OrientGene®) and complete an online questionnaire. The primary outcomes are the prevalence and incidence of antibodies against SARS-CoV-2 in PHCPs during a 12-month follow-up period. Secondary outcomes include the longevity of antibodies against SARS-CoV-2.Ethics and disseminationEthical approval has been granted by the Ethics Committee of the University Hospital Antwerp/University of Antwerp (Belgian registration number: 3002020000237). Alongside journal publications, dissemination activities include the publication of monthly reports to be shared with the participants and the general population through the publicly available website of the Belgian health authorities (Sciensano).RegistrationTrial registration number:NCT04779424Article summaryStrengths and limitations of this studyThis large cohort study will provide regular, timely and precise data at national level on prevalence and incidence of antibodies against SARS-CoV-2 among primary health care providers (PHCPs) managing the vast majority of COVID-19 and other patients and therefore essential to organise health care efficiently.This study will familiarise PHCPs with the use of serology-based point-of-care tests (POCTs) and validate the POCT in a primary care setting.Missing data points and the use of a convenience sample could limit the validity of the study results.

IntroductionIn the current SARS-CoV-2 pandemic, testing for SARS-CoV-2 specific antibodies is paramount to monitor immune responses in post-authorization vaccination and sero-epidemiology studies. However, large scale and iterative serological testing by venipuncture in older persons can be challenging. Capillary blood sampled using a finger prick and collected on protein saver cards, i.e., dried blood spots (DBS), has already proven to be a promising alternative. However, elderly persons have a reduced cutaneous microvasculature, which may affect DBS-based antibody testing. Therefore, we aimed to evaluate the performance of DBS for the detection of SARS-CoV-2 antibodies in nursing homes residents.Materials and methodsWe collected venous blood and paired Whatman and EUROIMMUN DBS from nursing home residents, and from staff as a reference population. Venous blood samples were analyzed for the presence of SARS-CoV-2 IgG antibodies using the Abbot chemiluminescent microparticle immunoassay (CMIA). DBS were analyzed by the EUROIMMUN enzyme-linked immuno sorbent assay (ELISA) for SARS-CoV-2 IgG antibodies. We performed a statistical assessment to optimize the ELISA cut-off value for the DBS using the Youden’s J index.ResultsA total of 273 paired DBS-serum samples were analyzed, of which 129 were positive as assessed by the reference test. The sensitivities and specificities of DBS ranged from 95.0% to 97.1% and from 97.1% to 98.8%, respectively, depending on population (residents or staff) or DBS card type.ConclusionDBS sampling is a valid alternative to venipuncture for the detection of SARS-CoV-2 antibodies in the elderly.

This is the twelfth version (eleventh update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline.What is the role of drugs in the treatment of patients with covid-19?The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and under way. The emerging SARS-CoV-2 variants (such as omicron) and subvariants are also changing the role of therapeutics. This update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers, and janus kinase (JAK) inhibitors in patients with severe or critical covid-19, and modifies previous recommendations for the neutralising monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe covid-19.• Remdesivir: a conditional recommendation for its use in patients with severe covid-19; and a conditional recommendation against its use in patients with critical covid-19. • Concomitant use of IL-6 receptor blockers (tocilizumab or sarilumab) and the JAK inhibitor baricitinib: these drugs may now be combined, in addition to corticosteroids, in patients with severe or critical covid-19. • Sotrovimab and casirivimab-imdevimab: strong recommendations against their use in patients with covid-19, replacing the previous conditional recommendations for their use.When moving from new evidence to updated recommendations, the Guideline Development Group (GDG) considered a combination of evidence assessing relative benefits and harms, values and preferences, and feasibility issues. For remdesivir, new trial data were added to a previous subgroup analysis and provided sufficiently trustworthy evidence to demonstrate benefits in patients with severe covid-19, but not critical covid-19. The GDG considered benefits of remdesivir to be modest and of moderate certainty for key outcomes such as mortality and mechanical ventilation, resulting in a conditional recommendation. For baricitinib, the GDG considered clinical trial evidence (RECOVERY) demonstrating reduced risk of death in patients already receiving corticosteroids and IL-6 receptor blockers. The GDG acknowledged that the clinical trials were not representative of the world population and that the risk-benefit balance may be less advantageous, particularly in patients who are immunosuppressed at higher risk of opportunistic infections (such as serious fungal, viral, or bacteria), those already deteriorating where less aggressive or stepwise addition of immunosuppressive medications may be preferred, and in areas where certain pathogens such as HIV or tuberculosis, are of concern. The panel anticipated that there would be situations where clinicians may opt for less aggressive immunosuppressive therapy or to combine medications in a stepwise fashion in patients who are deteriorating. The decision to combine the medications will depend on their availability, and the treating clinician's perception of the risk-benefit balance associated with combination immunosuppressive therapy, particularly in patient populations at risk of opportunistic infections who may have been under-represented in clinical trials. When making a strong recommendation against the use of monoclonal antibodies for patients with covid-19, the GDG considered in vitro neutralisation data demonstrating that sotrovimab and casirivimab-imdevimab evaluated in clinical trials have meaningfully reduced neutralisation activity of the currently circulating variants of SARS-CoV-2 and their subvariants. There was consensus among the panel that the absence of in vitro neutralisation activity strongly suggests absence of clinical effectiveness of these monoclonal antibodies. However, there was also consensus regarding the need for clinical trial evidence in order to confirm clinical efficacy of new monoclonal antibodies that reliably neutralise the circulating strains in vitro. Whether emerging new variants and subvariants might be susceptible to sotrovimab, casirivimab-imdevimab, or other anti-SARS-CoV-2 monoclonal antibodies cannot be predicted.• Recommended for patients with severe or critical covid-19—strong recommendations for systemic corticosteroids; IL-6 receptor blockers (tocilizumab or sarilumab) in combination with corticosteroids; and baricitinib as an alternative to IL-6 receptor blockers, in combination with corticosteroids. • Recommended for patients with non-severe covid-19 at highest risk of hospitalisation—a strong recommendation for nirmatrelvir/ritonavir; conditional recommendations for molnupiravir and remdesivir. • Not recommended for patients with non-severe covid-19—a conditional recommendation against systemic corticosteroids; a strong recommendation against convalescent plasma; a recommendation against fluvoxamine, except in the context of a clinical trial; and a strong recommendation against colchicine. • Not recommended for patients with non-severe covid-19 at low risk of hospitalisation—a conditional recommendation against nirmatrelvir/ritonavir. • Not recommended for patients with severe or critical covid-19—a recommendation against convalescent plasma except in the context of a clinical trial; and a conditional recommendation against the JAK inhibitors ruxolitinib and tofacitinib. • Not recommended, regardless of covid-19 disease severity—a strong recommendations against hydroxychloroquine and against lopinavir/ritonavir; and a recommendation against ivermectin except in the context of a clinical trial.This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact.Recommendations on anticoagulation are planned for the next update to this guideline.

Background Although heart failure (HF) patients often consider sexual activity as an essential aspect of their quality of life (QoL) and are usually uncertain if it is safe to perform sexual activity, this topic is overall poorly addressed in clinical practice. Aims The aim of this study was to explore the perceptions and practices of Flemish caregivers. Methods Healthcare providers were recruited through convenience sampling and filled in an adapted version of the UNITE Sexual Counselling Instrument. Several relevant network structures in Flanders were used to distribute the questionnaires-online as well as on paper-to healthcare workers being involved in the care to HF patients. Results Results of 180 participants indicated that 51.5% of the healthcare providers have never provided sexual counselling in HF patients. Being male, having a masters' degree, having more than 10 years of experience in cardiovascular disease, working in an ambulatory care department and having more positive attitudes were independently associated with a higher provision of sexual counselling in practice. Conclusion Although healthcare providers perceive it as their responsibility to discuss patients' sexual concerns, these issues are not often addressed in daily practice. Increasing knowledge in healthcare providers and specific practical training in providing information on sexual activity in HF patients are recommended. Further studies are needed to investigate how sexual counselling can be provided in agreement with HF patients' expectations and needs.

Background Depression and anxiety are the most frequent indication for which antidepressants are prescribed. Long-term antidepressant use is driving much of the internationally observed rise in antidepressant consumption. Surveys of antidepressant users suggest that 30% to 50% of long-term antidepressant prescriptions had no evidence-based indication. Unnecessary use of antidepressants puts people at risk of adverse events. However, high-certainty evidence is lacking regarding the effectiveness and safety of approaches to discontinuing long-term antidepressants. Objectives To assess the effectiveness and safety of approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. Search methods We searched all databases for randomised controlled trials (RCTs) until January 2020. Selection criteria We included RCTs comparing approaches to discontinuation with continuation of antidepressants (or usual care) for people with depression or anxiety who are prescribed antidepressants for at least six months. Interventions included discontinuation alone (abrupt or taper), discontinuation with psychological therapy support, and discontinuation with minimal intervention. Primary outcomes were successful discontinuation rate, relapse (as defined by authors of the original study), withdrawal symptoms, and adverse events. Secondary outcomes were depressive symptoms, anxiety symptoms, quality of life, social and occupational functioning, and severity of illness. Data collection and analysis We used standard methodological procedures as expected by Cochrane. Main results We included 33 studies involving 4995 participants. Nearly all studies were conducted in a specialist mental healthcare service and included participants with recurrent depression (i.e. two or more episodes of depression prior to discontinuation). All included trials were at high risk of bias. The main limitation of the review is bias due to confounding withdrawal symptoms with symptoms of relapse of depression. Withdrawal symptoms (such as low mood, dizziness) may have an effect on almost every outcome including adverse events, quality of life, social functioning, and severity of illness. Abrupt discontinuation Thirteen studies reported abrupt discontinuation of antidepressant. Very low-certainty evidence suggests that abrupt discontinuation without psychological support may increase risk of relapse(hazard ratio (HR) 2.09, 95% confidence interval (CI) 1.59 to 2.74; 1373 participants, 10 studies) and there is insufficient evidence of its effect on adverse events (odds ratio (OR) 1.11, 95% CI 0.62 to 1.99; 1012 participants, 7 studies; I-2 = 37%) compared to continuation of antidepressants, without specific assessment of withdrawal symptoms. Evidence about the effects of abrupt discontinuation on withdrawal symptoms (1 study) is very uncertain. None of these studies included successful discontinuation rate as a primary endpoint. Discontinuation by "taper" Eighteen studies examined discontinuation by "tapering" (one week or longer). Most tapering regimens lasted four weeks or less. Very low-certainty evidence suggests that "tapered" discontinuation may lead to higher risk of relapse (HR 2.97, 95% CI 2.24 to 3.93; 1546 participants, 13 studies) with no or little difference in adverse events (OR 1.06, 95% CI 0.82 to 1.38; 1479 participants, 7 studies; I-2 = 0%) compared to continuation of antidepressants, without specific assessment of withdrawal symptoms. Evidence about the effects of discontinuation on withdrawal symptoms (1 study) is very uncertain. Discontinuation with psychological support Four studies reported discontinuation with psychological support. Very low-certainty evidence suggests that initiation of preventive cognitive therapy (PCT), or MBCT, combined with "tapering" may result in successful discontinuation rates of 40% to 75% in the discontinuation group (690 participants, 3 studies). Data from control groups in these studies were requested but are not yet available. Low-certainty evidence suggests that discontinuation combined with psychological intervention may result in no or little effect on relapse (HR 0.89, 95% CI 0.66 to 1.19; 690 participants, 3 studies) compared to continuation of antidepressants. Withdrawal symptoms were not measured. Pooling data on adverse events was not possible due to insufficient information (3 studies). Discontinuation with minimal intervention Low-certainty evidence from one study suggests that a letter to the general practitioner (GP) to review antidepressant treatment may result in no or little effect on successful discontinuation rate compared to usual care (6% versus 8%; 146 participants, 1 study) or on relapse (relapse rate 26% vs 13%; 146 participants, 1 study). No data on withdrawal symptoms nor adverse events were provided. None of the studies used low-intensity psychological interventions such as online support or a changed pharmaceutical formulation that allows tapering with low doses over several months. Insufficient data were available for the majority of people taking antidepressants in the community (i.e. those with only one or no prior episode of depression), for people aged 65 years and older, and for people taking antidepressants for anxiety. Authors' conclusions Currently, relatively few studies have focused on approaches to discontinuation of long-term antidepressants. We cannot make any firm conclusions about effects and safety of the approaches studied to date. The true effect and safety are likely to be substantially different from the data presented due to assessment of relapse of depression that is confounded by withdrawal symptoms. All other outcomes are confounded with withdrawal symptoms. Most tapering regimens were limited to four weeks or less. In the studies with rapid tapering schemes the risk of withdrawal symptoms may be similar to studies using abrupt discontinuation which may influence the effectiveness of the interventions. Nearly all data come from people with recurrent depression. There is an urgent need for trials that adequately address withdrawal confounding bias, and carefully distinguish relapse from withdrawal symptoms. Future studies should report key outcomes such as successful discontinuation rate and should include populations with one or no prior depression episodes in primary care, older people, and people taking antidepressants for anxiety and use tapering schemes longer than 4 weeks.

AimsPatients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality.Method and resultsWe used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existent heart disease and in-hospital mortality. 16,511 patients with COVID-19 were included (21.1% aged 66 – 75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male and often had other comorbid conditions when compared to those without. Mortality was higher in patients with cardiac disease (29.7%; n=1545 versus 15.9%; n=1797). However, following multivariable adjustment this difference was not significant (adjusted risk ratio (aRR) 1.08 [95% CI 1.02 – 1.15; p-value 0.12 (corrected for multiple testing)]). Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure aRR (1.19 [1.10 – 1.30]; p-value ConclusionConsiderable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare.

Patient access to electronic health records gives rise to ethical questions related to the patient-doctor-computer relationship. Our study aims to examine patients’ moral attitudes toward a shared EHR, with a focus on autonomy, information access, and responsibility. A de novo self-administered questionnaire containing three vignettes and 15 statements was distributed among patients in four different settings. A total of 1688 valid questionnaires were collected. Patients’ mean age was 51 years, 61% was female, 50% had a higher degree (college or university), and almost 50% suffered from a chronic illness. Respondents were hesitant to hide sensitive information electronically from their care providers. They also strongly believed hiding information could negatively affect the quality of care provided. Participants preferred to be informed about negative test results in a face-to-face conversation, or would have every patient decide individually how they want to receive results. Patients generally had little experience using patient portal systems and expressed a need for more information on EHRs in this survey. They tended to be hesitant to take up control over their medical data in the EHR and deemed patients share a responsibility for the accuracy of information in their record.

In the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, testing for SARS-CoV-2-specific antibodies is paramount for monitoring immune responses in postauthorization vaccination and seroepidemiological studies. However, large-scale and iterative serological testing by venipuncture in older persons can be challenging. Capillary blood sampling using a finger prick and collection on protein saver cards, i.e., dried blood spots (DBSs), has already proven to be a promising alternative. However, elderly persons have reduced cutaneous microvasculature, which may affect DBS-based antibody testing. Therefore, we aimed to evaluate the performance of DBS tests for the detection of SARS-CoV-2 antibodies among nursing homes residents. We collected paired venous blood and DBS samples on two types of protein saver cards (Whatman and EUROIMMUN) from nursing home residents, as well as from staff members as a reference population. Venous blood samples were analyzed for the presence of SARS-CoV-2 IgG antibodies using the Abbott chemiluminescent microparticle immunoassay (CMIA). DBS samples were analyzed by the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for SARS-CoV-2 IgG antibodies. We performed a statistical assessment to optimize the ELISA cutoff value for the DBS testing using Youden's J index. A total of 273 paired DBS-serum samples were analyzed, of which 129 were positive, as assessed by the reference test. The sensitivities and specificities of DBS testing ranged from 95.0% to 97.1% and from 97.1% to 98.8%, respectively, depending on the population (residents or staff members) and the DBS card type. Therefore, we found that DBS sampling is a valid alternative to venipuncture for the detection of SARS-CoV-2 antibodies among elderly subjects. IMPORTANCE Since the implementation of newly developed SARS-CoV-2 vaccines in the general population, serological tests are of increasing importance. Because DBS samples can be obtained with a finger prick and can be shipped and stored at room temperature, they are optimal for use in large-scale SARS-CoV-2 serosurveillance or postauthorization vaccination studies, even in an elderly study population.

IntroductionAcute rhinosinusitis (ARS) is a prime reason for doctor visits and among the conditions with highest antibiotic overprescribing rates in adults. To reduce inappropriate prescribing, we aim to predict the absolute benefit of antibiotic treatment for individual adult patients with ARS by applying multivariable risk prediction methods to individual patient data (IPD) of multiple randomised placebo-controlled trials.Methods and analysisThis is an update and re-analysis of a 2008 IPD meta-analysis on antibiotics for adults with clinically diagnosed ARS. First, the reference list of the 2018 Cochrane review on antibiotics for ARS will be reviewed for relevant studies published since 2008. Next, the systematic searches of CENTRAL, MEDLINE and Embase of the Cochrane review will be updated to 1 September 2020. Methodological quality of eligible studies will be assessed using the Cochrane Risk of Bias 2 tool. The primary outcome is cure at 8–15 days. Regression-based methods will be used to model the risk of being cured based on relevant predictors and treatment, while accounting for clustering. Such model allows for risk predictions as a function of treatment and individual patient characteristics and hence gives insight into individualised absolute benefit. Candidate predictors will be based on literature, clinical reasoning and availability. Calibration and discrimination will be evaluated to assess model performance. Resampling techniques will be used to assess internal validation. In addition, internal–external cross-validation procedures will be used to inform on between-study differences and estimate out-of-sample model performance. Secondarily, we will study possible heterogeneity of treatment effect as a function of outcome risk.Ethics and disseminationIn this study, no identifiable patient data will be used. As such, the Medical Research Involving Humans Subject Act (WMO) does not apply and official ethical approval is not required. Results will be submitted for publication in international peer-reviewed journals.PROSPERO registration numberCRD42020220108.

Background Inappropriate laboratory test ordering poses an important burden for healthcare. Clinical decision support systems (CDSS) have been cited as promising tools to improve laboratory test ordering behavior. The objectives of this study were to evaluate the effects of an intervention that integrated a clinical decision support service into a computerized physician order entry (CPOE) on the appropriateness and volume of laboratory test ordering, and on diagnostic error in primary care. Methods This study was a pragmatic, cluster randomized, open-label, controlled clinical trial. Setting Two hundred eighty general practitioners (GPs) from 72 primary care practices in Belgium. Patients Patients aged ≥ 18 years with a laboratory test order for at least one of 17 indications: cardiovascular disease management, hypertension, check-up, chronic kidney disease (CKD), thyroid disease, type 2 diabetes mellitus, fatigue, anemia, liver disease, gout, suspicion of acute coronary syndrome (ACS), suspicion of lung embolism, rheumatoid arthritis, sexually transmitted infections (STI), acute diarrhea, chronic diarrhea, and follow-up of medication. Interventions The CDSS was integrated into a computerized physician order entry (CPOE) in the form of evidence-based order sets that suggested appropriate tests based on the indication provided by the general physician. Measurements The primary outcome of the ELMO study was the proportion of appropriate tests over the total number of ordered tests and inappropriately not-requested tests. Secondary outcomes of the ELMO study included diagnostic error, test volume, and cascade activities. Results CDSS increased the proportion of appropriate tests by 0.21 (95% CI 0.16–0.26, p < 0.0001) for all tests included in the study. GPs in the CDSS arm ordered 7 (7.15 (95% CI 3.37–10.93, p = 0.0002)) tests fewer per panel. CDSS did not increase diagnostic error. The absolute difference in proportions was a decrease of 0.66% (95% CI 1.4% decrease–0.05% increase) in possible diagnostic error. Conclusions A CDSS in the form of order sets, integrated within the CPOE improved appropriateness and decreased volume of laboratory test ordering without increasing diagnostic error. Trial registration ClinicalTrials.gov Identifier: NCT02950142, registered on October 25, 2016

International audience; Background: Infective endocarditis (IE) is a life-threatening disease. Despite advancements in diagnostic methods, the initial clinical presentation of IE remains a valuable asset. Therefore, the impact of clinical presentation on outcomes and its association with microorganisms and IE localization were assessed herein. Methods: This retrospective study included 183 patients (age 68.9 ± 14.2 years old, 68.9% men) with definite IE at two tertiary care hospitals in Belgium. Demographic data, medical history, clinical presentation, blood cultures, imaging data and outcomes were recorded. Results: In-hospital mortality rate was 22.4%. Sixty (32.8%) of the patients developed embolism, 42 (23%) shock, and 103 (56.3%) underwent surgery during hospitalization. Shock at admission predicted embolism during hospitalization (odds ratio [OR] 2.631, 95% confidence interval [CI] 1.119-6.184, p = 0.027). A new cardiac murmur at admission predicted cardiac surgery (OR 1.949, 95% CI 1.007-3.774, p = 0.048). Methicillin resistant Staphylococcus aureus predicted in-hospital mortality and shock (p = 0.005, OR 6.945, 95% CI 1.774-27.192 and p = 0.015, OR 4.691, 95% CI 1.348-16.322, respectively). Mitral valve and aortic valve IE respectively predicted in-hospital death (p = 0.039, OR 2.258, 95% CI 1.043-4.888) and embolism (p = 0.017, OR 2.328, 95% CI 1.163-4.659). Conclusions: In this retrospective study, shock at admission independently predicted embolism during hospitalization in IE patients. Moreover, a new cardiac murmur at admission predicted the need for cardiac surgery. This emphasizes the importance of a comprehensive initial clinical evaluation in combination with imaging and microbiological data, in order to identify high-risk IE patients early.

AimsMost patients with established atherosclerotic cardiovascular disease (CVD) are at very high risk for developing recurrent events. Since this risk varies a lot between patients there is a need to identify those in whom an even more intensive secondary prevention strategy should be envisaged. Using data from the EUROASPIRE IV and V cohorts of coronary heart disease (CHD) patients from 27 European countries, we aimed at developing and internally and externally validating a risk model predicting recurrent CVD events in patients aged < 75 years.Methods and resultsProspective data were available for 12 484 patients after a median follow-up time of 1.7 years. The primary endpoint, a composite of fatal CVD or new hospitalizations for non-fatal myocardial infarction (MI), stroke, heart failure, coronary artery bypass graft, or percutaneous coronary intervention (PCI), occurred in 1424 patients. The model was developed based on data from 8000 randomly selected patients in whom the association between potential risk factors and the incidence of the primary endpoint was investigated. This model was then validated in the remaining 4484 patients. The final multivariate model revealed a higher risk for the primary endpoint with increasing age, a previous hospitalization for stroke, heart failure or PCI, a previous diagnosis of peripheral artery disease, self-reported diabetes and its glycaemic control, higher non-high-density lipoprotein cholesterol, reduced renal function, symptoms of depression and anxiety and living in a higher risk country. The model demonstrated excellent internal validity and proved very adequate in the validation cohort. Regarding external validity, the model demonstrated good discriminative ability in 20 148 MI patients participating in the SWEDEHEART register. Finally, we developed a risk calculator to estimate risks at 1 and 2 years for patients with stable CHD.ConclusionIn patients with CHD, fatal and non-fatal rates of recurrent CVD events are high. However, there are still opportunities to optimize their management in order to prevent further disease or death. The EUROASPIRE Risk Calculator may be of help to reach this goal.

This study tested the effectiveness of HeartMan—a mobile personal health system offering decisional support for management of congestive heart failure (CHF)—on health-related quality of life (HRQoL), self-management, exercise capacity, illness perception, mental and sexual health. A randomized controlled proof-of-concept trial (1:2 ratio of control:intervention) was set up with ambulatory CHF patients in stable condition in Belgium and Italy. Data were collected by means of a 6-min walking test and a number of standardized questionnaire instruments. A total of 56 (34 intervention and 22 control group) participants completed the study (77% male; mean age 63 years, sd 10.5). All depression and anxiety dimensions decreased in the intervention group (p p p p

Contact and interactions between owners and their pets may have beneficial physical and social effects on people, but may also facilitate the transmission of zoonotic agents and resistant bacteria. To estimate the risk of these contacts, more information regarding the frequency and intensity of this physical contact is required. Therefore, an online survey was conducted among pet owners resulting in 701 completed questionnaires. Questions regarding the interactions between dogs and owners were linked with a score from 1 (limited interactions) to 3 (highly intense interactions). After scoring these self-reported interactions, a contact intensity score was calculated for each respondent by summing up the different allocated scores from all questions. This contact intensity score was used to identify predictors of more intense contact based on a multivariable linear regression model. Interactions between dogs and their owners were widespread (e.g., 85.3% of the dogs licked their owner&rsquo, s hand) and intense (e.g., 49.3% of owners reported being licked in the face). The gender, age, and place of residence (city, village, or countryside) of the respondent, together with the size and age of the dog, were significantly associated with the contact intensity score in the multivariable model. On average, female respondents younger than 65 years who lived in the city and had a small young dog had the most intense contact with it. Further research is necessary to evaluate the risk of these interactions in light of zoonotic and antimicrobial resistance transfer.

The novel coronavirus epidemic is transforming the world\ud in which we live. This pandemic will bring sweeping changes everywhere, not least in the field of primary care medicine. Like one of our colleagues said: ‘after this crisis, perhaps even our calendar needs to be redefined. From now on, “BC” might stand for “Before Coronavirus”’. This quote puts into perspective just how significant the current times are for our profession. In this editorial, we will discuss challenges and tasks the COVID-19 crisis presents for family medicine.

0, Brussels Collaboration on Bodily Integrity, info:eu-repo/semantics/published

Research question Does uterine activity differ in patients who have undergone successful IVF treatment compared with patients who have undergone unsuccessful IVF treatment? Design Prospective study of 16 women who underwent fresh single embryo transfer. All patients underwent transvaginal ultrasound in three phases of the IVF treatment: ovarian stimulation 1 h before embryo transfer (ET1) and 5–7 days after embryo transfer (ET5–7). Uterine motion analysis was implemented by a dedicated speckle tracking algorithm; frequency- and amplitude-related features were extracted from the derived signals to characterize the uterine activity in relation to ongoing implantation (positive HCG after 6 weeks) and ongoing pregnancy at 11 weeks. Results Uterine activity in terms of frequency (ovarian stimulation ET1, P = 0.04; ovarian stimulation ET5–7, P = 0.002) and amplitude (ovarian stimulation ET1, P = 0.0003; ovarian stimulation ET5–7, P = 0.000008) is significantly higher in the ovarian stimulation phase compared with ET1 and ET5–7. Women with ongoing pregnancies showed significantly higher uterine contraction frequency compared with those with no ongoing pregnancies in all phases (ovarian stimulation, P = 0.006; ET1, P = 0.015; ET5–7, P = 0.007). Uterine contraction amplitude was significantly lower (P = 0.037) in women at ET5–7 in women with ongoing pregnancies. Conclusions This study is a first step towards assessing uterine activity during IVF objectively and non-invasively. It is an essential step to understanding the previously suggested effect of contractions on IVF failure. Uterine activity after embryo transfer characterized by high frequency and low amplitude may favour embryo implantation. Research with larger patient cohorts is needed to build on current evidence and knowledge of uterine contractions during IVF.

ObjectiveThis study aimed to assess implementation adherence (how well the patient’s actual intake matches the prescribed dosing regimen) to non-vitamin K antagonist oral anticoagulants (NOACs) and to explore experiences with and beliefs about NOACs in a real-world sample of long-term NOAC users.MethodsA cross-sectional observational study was conducted in home-dwelling adults who started taking a NOAC at least 1 year prior to inclusion. Pharmacy dispensing data were used to calculate the Medication Possession Ratio (MPR). Patients were recruited in 158 community pharmacies in Flanders, Belgium. They completed a questionnaire collecting basic characteristics and exploring self-reported adherence to NOACs (using the Medication Adherence Report Scale, MARS) and experiences with and beliefs about NOACs (using the Beliefs about Medicines Questionnaire, BMQ).ResultsA total of 766 patients (mean age 76.2±8.8 years, median CHA2DS2-VASc score 4 (IQR=3–4)) were included. The majority (93.5%) used NOAC for stroke prevention in atrial fibrillation. The median MPR was 95.2% (IQR=87.8–99.7) which corresponds with half of the study population not taking their NOAC on at least 17 cumulative days per year. Almost 21% of participants reported non-adherence on the MARS (score ConclusionsOur data indicate that long-term NOAC users have high implementation adherence and a positive attitude towards NOAC therapy. However, taking into account patients’ thromboembolic risk and NOACs’ short half-lives, further optimisation of NOAC use seems warranted in this population.

Introduction Problematic benzodiazepine use is a global health issue. Although the adverse side effects of long-term use of benzodiazepines are well known, it remains difficult to implement interventions for discontinuation in primary care. Considering the success of blended care for the treatment of sleeping disorders and the support of substance use disorders, evidence suggests that a blended care approach, combining face-to-face consultations with the general practitioner with web-based self-learning by the patient, is beneficial for the discontinuation of chronic benzodiazepine use for primary insomnia in general practice. Therefore, the aim of this study is to evaluate the effectiveness of such an approach for the discontinuation of benzodiazepine and zolpidem, zopiclone and zaleplon drugs ((z-)BZD) use in the long term and evaluate the implementation process. Methods and analysis This study is a multicentre, pragmatic, cluster randomised controlled trial with 1200 patients, included by 120 general practitioners. Allocation to usual or blended care happens at the level of the general practice in a 1:1 ratio using a block randomisation system stratified per language. The study population consists of adult primary care patients who have been using (z-)BZD for primary insomnia on a daily basis for at least 6 months. Primary outcome measure is the proportion of patients that discontinued (z-)BZD at 12 months assessed by toxicological screening for (z-)BZD in urine. Secondary outcomes include discontinuation of (z-)BZD at 6 months, quality of life and the number of defined daily doses of (z-)BZD prescribed. Data will be collected using a study-specific online platform and analysed using the intention-to-treat approach. The process of implementing blended care will be evaluated in a nested study. Ethics and dissemination This trial was approved by the Ethics Committee for Research of UZ/KU Leuven (ref. S61194). Study results will be disseminated via open-access, peer-reviewed publications and conference presentations. Trial registration number NCT03937180., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Lesbian, gay, bisexual, trans and intersex (LGBTI) people experience significant health inequalities. Located within a European Commission funded pilot project, this paper presents a review of the health inequalities faced by LGBTI people and the barriers health professionals encounter when providing care. Methods A narrative synthesis of 57 papers including systematic reviews, narrative reviews, meta-analyses and primary research. Literature was searched in Cochrane, Campbell Collaboration, Web of Science, CINAHL, PsychINFO and Medline. The review was undertaken to promote understanding of the causes and range of inequalities, as well as how to reduce inequalities. Results LGBTI people are more likely to experience health inequalities due to heteronormativity or heterosexism, minority stress, experiences of victimization and discrimination, compounded by stigma. Inequalities pertaining to LGBTI health(care) vary depending on gender, age, income and disability as well as between LGBTI groupings. Gaps in the literature remain around how these factors intersect to influence health, with further large-scale research needed particularly regarding trans and intersex people. Conclusion Health inequalities can be addressed via changes in policy, research and in practice through health services that accommodate the needs of LGBTI people. With improved training to address gaps in their knowledge of LGBTI health and healthcare, health professionals should work in collaboration with LGBTI people to address a range of barriers that prevent access to care. Through structural change combined with increased knowledge and understanding, services can potentially become more inclusive and equally accessible to all.

ObjectiveAcute infection is the most common presentation of children to hospital. A minority of these infections are serious, but early recognition and adequate management are essential. We aimed to develop improved tools to assess children attending ambulatory hospital care, integrating clinical features with point-of-care C reactive protein (CRP).DesignProspective observational diagnostic study.Setting and patients5517 acutely ill children (1 month–16 years) presenting to 106 paediatricians at six outpatient clinics and six emergency departments in Belgium.Index testPoint-of-care CRP alongside vital signs and objective symptoms measurements.Main outcomeHospital admission for >24 hours with a serious infection ResultsAn algorithm was developed consisting of clinical features and CRP. This achieved 97.1% (95% CI 94.3% to 98.7%) sensitivity and 99.6% (95% CI 99.2% to 99.8%) negative predictive value, excluding serious infections in 36.4% of children. It stratifies patients into three groups based on CRP level: high-risk group with CRP >75 mg/L (26.8% risk of infection), intermediate-risk group with CRP 20–75 mg/L and at least one of seven clinical features (8.1%), and lower risk group with CRP ConclusionsConducting a CRP test may first enable children to be stratified into three risk groups, guiding assessment of clinical features that could be performed by junior doctors or nurses. In one-third of acutely ill children, the algorithm could exclude serious infection. Prospective validation of the algorithm is needed.Clinical trial registrationNCT02024282(post-results).

Polypharmacy results in adverse drug interactions, high pill burden, and medication costs. Stopping or diminishing potentially inappropriate medication (PIM), is complex . Data on the use of PIM in a primary care context are scarce and deprescribing barriers for general practitioners (GP) are underexplored.Describing the use of PIM in primary care at the end of life, and exploring the barriers for GPs to deprescribe.Retrospective chart review of 210 consecutive patients referred to a palliative home care service and semi-structured interviews with 11 GPs. Percentages were calculated on medication use, linear regression was done to evaluate the effect of diagnosis on PIM use. Thematic analysis was used to analyze the interviews.In total 83 % of patients took at least one PIM. The proportion that continued taking PIMs at the time of referral, one week prior to death and at the day of dying: varies between 6% and 45% according to drug category. Linear regression showed a statistical significant (p 0.001) higher number of PIM use with non-cancer patients (mean 3,1-SD 1,5) than with cancer patients (mean 1,6-SD 1,6). Participants reported being aware of the PIM use, making efforts to deprescribe. Main issues GPs are taking into account are medical, communicative, and collaborative in nature.This study confirms the high level of PIM use in primary care at the end of life. The views of GPs inspire support strategies for deprescribing focusing on shared decision-making with patients and on interprofessional collaboration.

Background The effect of adherence to cardiac rehabilitation (CR) on outcome is not clear. Therefore, we aimed to assess the impact of drop-out for non-medical reasons of CR on event-free survival in coronary artery disease (CAD). Methods A total of 876 patients who attended CR after acute coronary syndrome (ACS), percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) were included. Drop-out was defined as attending ≤50% of the training sessions. A combined endpoint of all-cause mortality and rehospitalization for a cardiovascular event was used to specify event-free survival. Differences in clinical characteristics were assessed and parameters with p Results A total of 15% died or had a cardiovascular event during a median follow-up period of 33 months (interquartile range 24, 51). Overall, 17% dropped out before finishing half of the program. Patients who withdrew prematurely had a risk twice as high for a cardiovascular event or death (hazard ratio 1.92, 95% confidence interval 1.28–2.90) than those who attended more than half of the sessions. Both ACS (2.36, 1.47–3.58) and PCI (2.20, 1.22–3.96), as primary indicators for CR, were associated with an adverse outcome and also a prior history of chronic heart failure (CHF) remained negatively associated with event-free survival (3.67, 1.24–10.91). Finally, the presence of hyperlipidemia was independently related to a worse outcome (1.48, 1.02–2.16). Conclusions Drop-out for non-medical reasons was independently associated with a negative outcome in CAD. Therefore, underlying factors for drop-out should gain more attention in future research and should be taken into account when organizing CR.

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Objective To describe the decisions lesbian couples make when creating a family through donor insemination [DI] and to explore the negotiations between the biological and the non-biological mother. Methods We included 18 lesbian parents (9 biological and 9 non-biological mothers) with at least one child (7–10 years old) conceived through anonymous DI. We conducted in-depth semi-structured couple interviews at the participants' homes or at the Department of Reproductive Medicine of Ghent University Hospital (Belgium) where participants were treated in the past. The data were analysed using step-by-step inductive thematic analysis based on Braun and Clarke. Results Lesbian couples were confronted with decisions related to two themes: (1) the fertility treatment and (2) the organisation of the family. In this paper we focused on three particular decisions: whether or not to go through treatment together, the acceptance of an anonymous sperm donor, and the celebration of Mother's and Father's Days. Several decisions were linked to the heteronormative social context. The lesbian couples seemed to want to adapt as much as possible to this frame. Conclusion Heteronormativity and the genetic link between parent and child influenced the decision making in lesbian couples creating a family through DI.

STUDY QUESTION Is a stepwise change management approach an efficacious method to move from a Day 3 transfer policy to a Day 5 transfer policy for all patients in an IVF program? SUMMARY ANSWER A stepwise change from a Day 3 to a Day 5 transfer policy maintained the live birth rates per oocyte collection cycle (OCC) of the IVF program, with increased single embryo transfer (SET) and reduction of twin pregnancies. WHAT IS KNOWN ALREADY Evidence has shown that the probability of a live birth following IVF with a fresh embryo transfer (ET) is significantly higher after blastocyst-stage transfer than after cleavage-stage transfer. Blastocyst culture and transfer are usually performed in cases of good prognosis patients but many centers keep transferring cleavage-stage embryos for most of their patients because of the higher transfer cancelation rate in a blastocyst transfer policy. STUDY DESIGN, SIZE, DURATION In January 2012, a Day 5 embryo culture and blastocyst transfer policy including vitrification of supernumerary Day 5 blastocysts were implemented in a stepwise approach. The retrospective descriptive single-center analysis involving a preintervention phase consisted of Day 3 ETs and Day 3 slow freezing from 2010 until 2012. The postintervention phase involved a 6-year period from 2012 until 2017 in which three consecutive changes in the transfer policy were made, each over a 2-year period, based on the number of zygotes on Day 1. The primary outcome was live birth delivery rate per OCC during the stepwise change. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients with at least one zygote available on Day 1 were scheduled for a fresh transfer, either on Day 3 or 5. Cycles with preimplantation genetic testing, freeze-all and oocyte donation cycles and cycles with a Day 2 transfer in the preintervention period were excluded. In the preintervention group, all cycles were scheduled for Day 3 transfer (n = 671 OCC) and slow freezing of the remaining Day 3 embryos. In the postintervention period, three periods were analyzed: period 1 (n = 1510 OCC; 1–9 zygotes: Day 3 transfer and >9 zygotes: Day 5 transfer); period 2 (n = 1456 OCC; 1–4 zygotes: Day 3 transfer and >4 zygotes: Day 5 transfer) and period 3 (n = 1764 OCC; Day 5 transfer). All remaining embryos underwent extend culture and were vitrified on Day 5, if developed to at least an early blastocyst. Data were analyzed using a mixed regression model with patient as a random factor. MAIN RESULTS AND THE ROLE OF CHANCE In the preintervention group, all OCC were scheduled for a Day 3 transfer. In period 1, period 2 and period 3, 20.9%, 61.5% and 100% of the OCCs were scheduled for a Day 5 transfer, respectively. More transfers per OCC were canceled in the postintervention period 2 and period 3 compared to the preintervention period (5.3% and 18.7% versus 3.4%, respectively; P Pregnancy and live birth delivery rate per fresh transfer, respectively, were significantly lower in the preintervention group (26.7% and 19.1%) as compared to period 3 (39.3% and 24.2%) (P LIMITATIONS, REASONS FOR CAUTION The primary limitation is the retrospective design of the study. The allocation of the cycles was done by the number of zygotes available without taking into account both embryological and clinical prognostic factors. Furthermore, the analysis was restricted to cycles where the standard transfer policy was followed. Embryos which were in the morula or compaction stage were not vitrified or cultured to Day 6, which could have contributed to the slight, not statistically significant, drop in live birth rate per OCC in group 3. WIDER IMPLICATIONS OF THE FINDINGS Live birth and cumulative live birth delivery rate per OCC in an unselected patient population is maintained in a Day 5 transfer policy compared to a Day 3 transfer policy. Additionally, a significantly reduction in twin pregnancy rate and a significant increase in SET were observed in a Day 5 transfer policy. For centers wanting to make the step from Day 3 to Day 5, this study provides a practical stepwise change management approach. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER None.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. To assess the feasibility and safety of discontinuation of long-term antidepressant use for depressive and anxiety disorders in adults aged over 18 years.

Background Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. Methods We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. Findings Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20–1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74–1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30–1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00–5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. Interpretation Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2–3 days sooner. Funding European Commission's Seventh Framework Programme.

Background Despite improvements in medical and surgical therapy, infective endocarditis (IE) remains a deadly disease. Echocardiography is the first-line diagnostic tool. However, data regarding its role in the prognostic assessment of in-hospital clinical outcome of IE are scarce. Purpose We sought to assess the role of echocardiography to predict the in-hospital outcome in a large cohort of patients diagnosed with definite IE and its association with clinical presentation and microorganisms. Methods We retrospectively included patients from two centers between 2006 and 2018. Transthoracic and transesophageal echocardiography were performed in all patients. The clinical endpoints were in-hospital death, embolic events (cerebrovascular and non-cerebrovascular), shock (septic shock and cardiogenic shock) and cardiac surgery. Results 183 patients with definite IE (age 68.9 ± 14.2 years old, 68.9% male) were evaluated. Ninety three (50.8%) patients had aortic valve IE and 81 (44.3%) patients presented with mitral valve IE. Twenty three patients had multivalvular IE. The in-hospital mortality rate was 22.4%. Sixty patients (32.8%) had embolic events and 42 (23%) patients developed shock during hospitalization. Surgery was performed in 103 (56.3%) patients. Mitral valve IE on echocardiography was an independent predictor of in-hospital mortality (p = 0.038, OR 0.38, 95% CI 0.15 – 0.94) and aortic valve IE on echocardiography was an independent predictor of embolic events (p = 0.018, OR 0.36, 95% 0.16-0.84). The presence of a new cardiac murmur upon admission was predictive for the need of cardiac surgery (p = 0.042, OR 0.51, 95% CI 0.22- 1.09) and correlated with the severity of valvular regurgitation identified by echocardiography (p = 0.024). Methicillin resistant Staphylococcus aureus (MRSA) as the causative microorganism was an independent predictor for in - hospital mortality and for the development of shock during hospitalization (p = 0.010, OR 0.13 95% CI 0.30 - 0.62 and p = 0.027, OR 6.11, 95% CI 1.22 – 30.37, respectively). No correlation was found between MRSA and echocardiographic parameters. Conclusion Mitral valve IE was an independent predictor of in - hospital mortality. Furthermore, aortic valve IE was an independent predictor of embolic events. The presence of a new cardiac murmur was predictive for the need of cardiac surgery and correlated with the severity of valvular regurgitation by echocardiography. Our findings suggest that a thorough physical examination upon admission is required in combination with a comprehensive echocardiographic exam for early identification of patients with IE at high - risk for in-hospital death and complications.

AimsOral anticoagulants (OACs) are crucial for treating atrial fibrillation (AF) patients at high thromboembolic risk. However, in AF patients at intermediate thromboembolic risk with a single non-sex-related stroke risk factor (CHA2DS2-VASc score 1 in men, 2 in women), guidelines advise to consider starting anticoagulation, which may result in OAC non-initiation due to underestimation of the thromboembolic risk of a single stroke risk factor and overestimation of the OAC-related bleeding risk. A critical appraisal of the role of OACs and the benefit–risk profile of non-vitamin K antagonist oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in this patient subgroup are needed.Methods and resultsThis systematic review provides an overview of literature on the effectiveness and safety of OACs in AF patients with a single non-sex-related stroke risk factor after searching Medline and Embase. Differences between individual stroke risk factors regarding the ischaemic stroke risk in non-anticoagulated AF patients are identified in a meta-analysis, demonstrating the highest increased risk in patients aged 65–74 years old or with diabetes mellitus, followed by heart failure, hypertension and vascular disease. Furthermore, meta-analysis results favour NOACs over VKAs, given their equal effectiveness and superior safety in AF patients at intermediate thromboembolic risk (HR 0.93, 95% CI 0.65 to 1.34 for stroke or systemic embolism; HR 0.60, 95% CI 0.45 to 0.80 for major bleeding; HR 0.48, 95% CI 0.14 to 1.59 for intracranial bleeding; HR 0.58, 95% CI 0.47 to 0.71 for mortality).ConclusionOur systematic review with meta-analysis favours the use of anticoagulation in AF patients with a single non-sex-related stroke risk factor, especially when age ≥65 years or diabetes mellitus is present, with a preference for NOACs over VKAs.

Background: Familial hypercholesterolaemia (FH) is underdiagnosed in most countries. We report our first experience from a national pilot project of cascade screening in relatives of FH patients. Methodology: Participating specialists recruited consecutive index patients (IP) with Dutch Lipid Clinic Network (DLCN) score ≥6. After informed consent, the relatives were visited by the nurses to collect relevant clinical data and perform blood sampling for lipid profile measurement. FH diagnosis in the relatives was based on the DLCN and/or MEDPED FH (Make-Early-Diagnosis-to-Prevent-Early-Deaths-in-FH) criteria. Results: In a period of 18 months, a total of 127 IP (90 with definite FH and 37 with probable FH) were enrolled in 15 centres. Out of the 270 relatives visited by the nurses, 105 were suspected of having FH: 31 with DCLN score >8, 33 with DLCN score 5-8 and 41 with MEDPED FH criteria. In a post-hoc analysis, another set of MEDPED FH criteria established in the Netherlands and adapted to Belgium allowed to detect FH in 51 additional relatives. Conclusion: In a country with no national FH screening program, our pilot project demonstrated that implementing a simple phenotypical FH cascade screening strategy using the collaboration of motivated specialists and two nurses, allowed to diagnose FH in 127 index patients and an additional 105 of their relatives over the two-year period. Newly developed MEDPED FH cut-offs, easily applicable by a nurse with a single blood sample, might further improve the sensitivity of detecting FH within families., SCOPUS: ar.j, info:eu-repo/semantics/published